Newsletter of the Center for Proton Therapy :: Paul Scherrer Institut :: March 2016 :: # 8 :: page 1
SpotOn+
Center for Proton Therapy :: Paul Scherrer Institut :: # 8_3/2016
Dear Colleagues
In this Q1 2016 edition of our SpotOn+ newsletter,
Schalenbourg and Prof. L. Zografos in Lausanne
operative implants treated with protons have a
these challenging mobile tumors is to use a
(Hôpital Ophtalmique Jules-Gonin). It is interest-
significantly (p<0.05) lower overall survival than
combined dose-disruption mitigation strategy,
ing to note that the majority of centers (80%) those without any metal implant. This is in line namely re-scanning and gating in the not too
Dr. Jan Hrbacek reports on the results of an in- uses a treatment planning system that is not with the data from Boston and it is currently distant future. This would be possible using our ternational survey on ocular proton therapy that supported by any vendors at the present time.
unclear if metal implants do compromise proton
up-graded treatment platform of Gantry 2 and
was initiated by PSI within the framework of the This raises interesting questions so as how to
radiation or if it is merely a proxy of more aggres-
Gantry 3, the latter being operational at the end
OPTIC working party of the PTCOG (www.ptcog. support & upgrade such a planning platform in
sive disease. Simulation studies performed at of this year. It is the believe of PSI that protons
ch). It was initially discussed within this group
the future, with no support from industry and it PSI using dedicated phantoms suggest however should not be only reserved to ‘niche’ indications
that protons for ocular oncology needed some is doubtful that we will find easy & quick answers that the former could not be a major detrimental but could benefit a substantial number of cancer added visibility, as this treatment modality is to this challenge. The second article reports on factor on survivorship and other factors, such as patients that have to be properly selected. This indeed a highly effective treatment in terms of the results of PBS proton therapy for extra-cranial delineation issues during the planning process, tumor control and eye-retention for uveal mela-
then will be clearly debated in our European
chordomas and chondrosarcomas. This analysis are possibly more relevant. In the last section of radiation oncology community as a number of
nomas (UM) and other ocular tumors. PSI has was co-performed by Dr. J.W. Snider (University this newsletter, the interplay effect of motion on treated over 6’000 patients, which represents of Maryland, USA) and Dr. Ralf Schneider. The
proton/carbon beam therapy centers will come
PBS protons is assessed using our LuCa phantom on line between 2018 and 2020.
22% of all UM patients treated worldwide with
outcome of patients with these spinal tumors is which is displayed in the summary. The figures
protons. This remarkable achievement over many
good, with 2/3 of patients surviving at 5 years show clearly that gating alone is probably not
Yours sincerely,
decades has been only possible with the clinical after the radiation therapy. For the first time, we appropriate to treat mobile tumors with scanned
Prof. Damien Charles Weber,
and scientific collaboration of the team of Dr.Ann
have been able to show that patients with post-
protons. As such, the current PSI strategy to treat
Chairman of CPT
Newsletter of the Center for Proton Therapy :: Paul Scherrer Institut :: March 2016 :: # 8 :: page 2
Table 1: Alphabetical list of ocular proton therapy centers participating in the survey
Radio-Oncology News Ocular Proton Therapy International Community Survey Ocular Proton Therapy International patients treated by centers from 2012
but one center deliver four fractions
Community (OPTIC), a sub-committee to 2014 and in total. The yearly accrual over a week, and the dose prescription
• BC Cancer Agency – TRIUMF, Vancouver, Canada • Center for Proton Therapy, Paul Scherrer Institut, Villigen, Switzerland • Centre Antoine-Lacassagne, Nice, France • Centre de Protonthérapie d’Orsay, Institut Curie, Orsay, France • Clatterbridge Cancer Centre, UK • F.H. Burr Proton Therapy Center, Massachusetts General Hospital, Boston, MA, USA
• Institute of Nuclear Physics, Polish Academy of Sciences, Krakow, Poland • Protons for Therapy, HelmholtzZentrum Berlin, Berlin, Germany in cooperation with BerlinProtonen am HZB, Charité – Universitätsmedizin Berlin, Berlin, Germany • UCSF Ocular Tumor Proton Therapy Program – University of California San Francisco at Davis, CA, USA • University of Florida Proton Therapy Institute, Jacksonville, FL, USA
of Particle Therapy Co-Operative Group
of all centers is approx. 1’500 patients.
was relatively homogeneous across
(PTCOG), organized the questionnaire
CPT PSI, with the total of 6’369 pa-
centers (56–60 Gy RBE). Likewise, the
survey to carry out a comparative anal-
tients (22%), remains the center with
dose prescription was 18–24 Gy RBE in
ysis of the treatment, human and tech-
the largest cohort of patients treated 2–4 fractions for age-related macular photography registered to the fundus to ±0.5mm (median ±0.3mm) and from
nical resources allotment, QA pro-
worldwide.
the position of a CTV using a fundus passing criteria ranging from ±0.1mm
degeneration. Dose prescription for on the geometrical model.
±0.5% to ±3.0% (median ±2%), respec-
gram, and follow-up strategies of
conjunctival melanoma differed sub-
tively. All centers required highly accu-
centers performing this highly special-
Indication & fractionation regime: The stantially, with dose and fraction num-
Technical: All centers used a cyclotron
rate coincidence of the imaging system
ized treatment.
most common ocular treatment for all ber ranging from 20.4 to 70.0 Gy RBE to accelerate protons, in combination
with the treatment iso-center, ranging
centers was uveal melanoma (UM). In Patient numbers: Ten centers partici-
in 4 to 8 fractions, respectively.
with dedicated horizontal beam lines from ±0.1mm to ±0.5mm. While toler-
addition, centers treated other primary
only, and with robotic chairs. Protons ance for other tests such as modula-
pating in the survey (Table 1) treated ocular malignancies, benign ocular
Treatment planning: The majority of were accelerated to energies of 60– tion, coincidence between imaging and
a combined 28’891 patient by the end tumors, choroidal metastases, con-
centers (80%) used EyePlan treatment 520 MeV. All multi-room centers (50%) treatment coordinate systems, and
of 2014. This corresponds to 98.8% of junctival tumors, and retinoblastomas. planning system (TPS), software deocular proton therapy patients world-
Half of the centers had treated also
accelerated to energy higher or equal beam’s flatness/symmetry was com-
veloped and maintained by a collab- to 230 MeV with subsequent degrada-
wide. Figure 1 details the number of pediatric patients. For UM patients, all orative effort amongst several re-
parable, the frequency of these tests
tion. Energy of protons entering into a varied anywhere between daily to
search centers for OPT (Massachusetts nozzle was degraded to 58–105 MeV yearly. Patient specific verification was 400
7000
General Hospital, Paul Scherrer Insti- (mean, 68 MeV) for clinical treatment. performed by 90 % of the centers
350
6000
tute, Clatterbridge Cancer Centre). All All centers position patients using checking dose, range, and modulation.
300
4000
200 3000
150
2000
100
1000
50 0
centers used a geometrical eye model. orthogonal x-ray imaging. Patient
5000
250
1
2
3
4
5
6
7
8
9
10
2012
222
310
269
115
146
225
123
9
4
5
2013
198
332
253
119
149
228
106
5
24
20
2014
215
351
266
127
179
213
108
7
46
24
total
6369
5433
5205
4689
2625
2525
1729
182
85
49
0
patients total
patients/year
Figure 1: Number of eye patients treated with proton therapy by 10 centers in total and in last three years (sorted in descending order by number of total number of patients)
Parameters of the geometrical model treatment time slots for set-up and Additional details of the survey and diswere primarily based on ultrasound (8 delivery ranged from 20 to 90 minutes cussion of the results may be found in centers), however, CT (5 centers) and (median 30 minutes). Manual treat-
http://dx.doi.org/10.1016/
MRI (4 centers) were used frequently ment gating was performed by a ma- j.ijrobp.2016.01.040 as well. For intraocular tumors, all jority (90 %) of centers to carefully centers defined clinical target volume
track intra-fractional motion of the eye. For any further information, please refer to CPT,
(CTV) based on transillumination dur-
ing ophthalmic surgery in combination QA: Most centers (90%) would check Dr. Jan Hrbacek with ultrasound (A- and B-scan) exam-
on a daily basis the range and the dose Tel. +41 56 310 37 36
ination. Most centers (90 %) verified (in water or other material) with the
jan.hrbacek.psi.ch
Newsletter of the Center for Proton Therapy :: Paul Scherrer Institut :: March 2016 :: # 8 :: page 3
Radio-Oncology News Long-term follow-up and clinical outcomes of patients treated for extracranial chordomas and chondrosarcomas
Axial, coronal, and sagittal images of a representative treatment plan to 74 Gy for a cervical chordoma.
with pencil beam scanning proton therapy at PSI Tumors of the spine and paraspinal regions re- underwent radiotherapy a second time for new main a challenge for surgeons and oncologists lesions (n=136), met the selection criteria. alike. Chordomas and chondrosarcomas are rare, This sample included 102 chordomas and 34 locally aggressive, and devastating tumors that chondrosarcomas, distributed throughout the commonly arise extracranially in close proximity spinal column and pelvis: cervical (n=57), thoto or involving the spinal column. For neurosur-
racic (n=24), lumbar (n=12), sacral (n=39) spine,
geons, the juxtaposition of these tumors often
and pelvis (n=4). Patients ranged in age from 22
necessitates subtotal or intralesional resection
to 81 (median=54). As expected, despite and The cause for this correlation remains unclear issues surrounding surgical stabilization. We are
followed frequently by surgical stabilization. For
due to the typically aggressive resections, 60% as in vitro measurements at PSI have demon- currently also investigating alternative stabili-
radiation oncologists, the particular proximity to of patients presented for proton therapy with
strated impressively reliable delivery of therapy zation materials and their effects on proton
the spinal cord complicates the delivery of ade-
gross residual disease, and 40% of patients despite the presence of such material (Dietlicher treatment planning in conjunction with corporate
quate adjuvant radiotherapy. For safely achieving
required metal implant surgical stabilization
et al. 2014). It is conceivable that worse/larger
partners. Results have been submitted to the
the particularly high doses required (often 70–74 prior to radiation. Though patients, during the initial disease or more complicated lesions ne-
55 th Annual Conference of the Particle Therapy
Gy) to sterilize these tumors, proton therapy, and early experience at PSI, were sometimes treated cessitate such stabilization and that patients Co-Operative Group, which will be held in May in particular pencil beam scanning proton ther-
with mixed modality (photon-proton) tech-
with such disease will, on average, fail more
in Prague.
apy, has proven particularly well-suited. Previous niques, 85 % (n=116) of the patients in this often. However, further investigation is required and underway to clarify this issue. Encourag-
Reference: Dietlicher et al: The effect of surgical
have demonstrated the safety and efficacy of this therapy exclusively. For the entire cohort, me- ingly, the toxicity of adjuvant proton radiother-
titanium rods on proton therapy delivered for
reports from our institution (Staab et al. 2011) approach in small sample sizes.
analysis received pencil beam scanning proton dian follow-up was 63 months.
apy remained exceedingly low despite the high cervical bone tumors: experimental validation
These initial outcomes also raised substantial Despite historical controls reporting particularly doses delivered. Grade 3 or higher toxicity was using an anthropomorphic phantom; http:// experienced in only 6 % and 5 % of cases in the
concerns regarding worsened outcomes in pa-
poor local control in this disease, especially with
tients with metal implant, surgical stabilization.
lower dose, photon techniques, five year local acute and late settings, respectively.
dx.doi.org/10.1088/0031-9155/59/23/7181 Staab et al: Spot-scanning based proton
Recently, we updated the center’s experience control, progression-free survival, and overall With long-term follow-up and a much larger therapy for extracranial chordoma; utilizing pencil beam scanning therapy in these survival in this study were an impressive 63%,
patient sample, pencil beam scanning proton
http://dx.doi.org/10.1016/j.ijrobp.2011.02.018
diseases, having treated now over 130 patients 57%, and 77 %, respectively. Surgical stabiliza- therapy has once again proven an effective and with extracranial chordoma or chondrosarcoma. tion remained an important prognostic factor in safe method for controlling these insidious tu-
For any further information,
Patients were only included in this new analysis determining outcomes, especially in patients mors. Promising further analysis is ongoing in
please refer to CPT,
if they had at least one year of follow-up and were
with chordoma, and overall survival was 49% an attempt to identify patients with higher-risk Dr. Ralf Schneider
adults. Spanning 18 years of treatment, from 1997 versus 66% at five years with and without metal disease that may benefit from further intensified Tel. +41 56 310 3789 to 2015, 133 patients, including 3 patients that implant (p< 0.05).
therapy and to evaluate strategies for mitigating
ralf.schneider@psi.ch
Newsletter of the Center for Proton Therapy :: Paul Scherrer Institut :: March 2016 :: # 8 :: page 4
Medical-Physics News Optical tracking of breathing motion for gated treatment with PBS proton therapy Intra-fractional motion is a major issue a customised solution for real-time for proton therapy delivered using pen-
A spherical GTV (3 cm diameter) was ning (3 rescans), no motion mitigation For any further information,
monitoring of breathing motion using contoured on the end-exhale phase of and stationary delivery, holding the
please refer to CPT,
a 4D-CT scan, acquired for treatment phantom at the end-exhale position.
Dr. Giovanni Fattori
cil beam scanning, limiting its precision optical tracking technology. The Pola-
for certain clinical indications. The ris SPECTRA position sensor (Northern planning. The internal target volume problem is of critical importance in the
treatment of patients with thoracic and integrated in the Gantry 2 facility and, abdominal tumours, where the breath-
Dose distortions found in the
Digital Inc. (Waterloo, CA)) has been (ITV) was then the GTV extended by non-compensated case (V95 = 49 %; 5mm towards the peak-inhale phase,
giovanni.fattori@psi.ch
D5-D95 =33%, γ3%/3mm=40%) are
mounted on the treatment couch, is and the ITV was extended isotropically partially mitigated by beam gating Dr. Rosalind Perrin
ing induced motion of anatomical used to precisely localize infrared re-
by another 5 mm to produce the PTV. (V95 = 62 %; D5-D95 = 13.5 %, γ3 % /
structures is large and interplays with
flective spheres (Fig. 1). Relying on the The average-image computed from all 3mm=60%). Furthermore, target cov-
the dynamics of treatment delivery.
correlation between target motion and the 4D-CT phases was used to optimize erage is almost restored when coupled
In conventional radiotherapy, dedi-
the displacement of the patient sur-
a single anterior-posterior field to give
cated strategies for breathing synchro-
face, a configuration of external mark-
a uniform dose of 1 Gy to the PTV. Before D95=17%, γ3%/3mm=82%). In the latter case however, homogeneity was
was verified matching the end-exhale
worse than for the stationary case
target motion during irradiation by The delivery of gated treatments has anatomy in the planning images with
(V95 = 86 %; D5-D95 = 12 %, γ3 % /
a stationary 3D scan acquired in-room
3mm=79%), indicating some residual
and involve either the limitation of until the correct geometry is detected. means of gating, breath-hold or by been verified in an experimental envidirect tumours tracking. The transfer
ronment close to the clinical scenario by means of 3D volumetric image reg-
motion effects.
of such knowledge to proton therapy,
that uses an anthropomorphic breath- istration. Phantom motions were mon-
Experimental film measurements
however, requires additional efforts ing phantom. A programmable ventila-
itored by tracking a single marker po-
showed that gating-plus-rescanning
tor was used to generate a realistic sition on the skin surface to selectively could recover the dose coverage at
tion-induced range uncertainties and pressure curve, resulting in 10 mm and deliver beam at the end-exhale phase.
95 % prescribed dose (Figure 2) and
daily deviations in the motion pattern. 2 mm peak-to-peak amplitudes for the
Moreover, to mitigate the target resid-
provide improved correspondence to
In this direction, we have developed tumour and skin surface respectively.
ual motion in the gating window, lim- the static case when evaluated using ited to maximum 4 mm in our experi- 3%/3mm gamma analysis. In the per-
rosalind.perrin@psi.ch
Imprint Editor Dr. Ulrike Kliebsch Chairman Prof. Damien C. Weber Chief Medical Physicist Prof. Tony Lomax Design and Layout Monika Blétry
Contact
ning. Four motion mitigation strategies internal-external motion correlation
Center for Proton Therapy CH-5232 Villigen PSI protonentherapie@psi.ch www.protonentherapie.ch Tel. +41 56 310 35 24 Fax +41 56 310 35 15
were tested: gated, gated-plus-rescan-
Villigen PSI, March 2016
mental setup, and the physiological spective of the clinical use of gating, instability of internal-external correla-
future activities will focus on robust
tion expected in the clinical scenario, breathing phase detection and synbeam gating was coupled with rescan-
Figure 1: (left panel) experimental setup; (right panel) definition of PTV (yellow) from ITV (blue) and GTV (red).
Tel. +41 56 310 50 24
with rescanning (V95 = 95 %; D5-
nized treatments are well established ers is used to pause the beam delivery irradiation, the phantom positioning
to take into account residual mo-
Tel. +41 56 310 36 85
chronized x-ray imaging to verify the on a daily basis.
Figure 2: measured film dose distributions (normalised to the mean ITV dose ‘Stationary’) in the central plane of the tumour. Film edge and ITV delineated in black, and white dashed contours, respectively.